Project Summary Glaucoma is a leading cause of vision morbidity and blindness worldwide. Early disease detection and sensitive monitoring of progression are crucial to allow timely treatment for preservation of vision. The introduction of ocular imaging technologies significantly improves these capabilities, but in clinical practice there are still substantial challenges at managing the optimal care for individual cases due to difficulties of accurately assessing the potential progression and its speed and magnitude. These difficulties are due to a variety of causes that change over the course of the disease, including large inter-subject variability, inherent measurement variability, image quality, varying dynamic ranges of measurements, minimal measurable level of tissues, etc. In this proposal, we propose novel agnostic data-driven deep learning approaches to detect glaucoma and accurately forecast its progression that are optimized to each individual case. We will use state- of-the-art automated computerized machine learning methods, namely the deep learning approach, to identify structural features embedded within OCT images that are associated with glaucoma and its progression without any a priori assumptions. This will provide novel insight into structural information, and has shown very encouraging preliminary results. Instead of relying on the conventional knowledge-based approaches (e.g. quantifying tissues known to be significantly associated with glaucoma such as retinal nerve fiber layer), the proposed cutting-edge agnostic deep learning approaches determine the features responsible for future structural and functional changes out of thousands of features autonomously by learning from the provided large longitudinal dataset. This program will advance the use of structural and functional information obtained in the clinics with a substantial impact on the clinical management of subjects with glaucoma. Furthermore, the developed methods have potentials to be applied to various clinical applications beyond glaucoma and ophthalmology.